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Cardio IQ Omega-3 and -6 Fatty Acids

Cardio IQ Omega-3 and -6 Fatty Acids

Test Summary

Cardio IQ® Omega-3 and -6 Fatty Acids


Clinical Use

  • Determine fatty acid-associated risk for cardiovascular events

  • Screen for omega-3 fatty acid deficiency

  • Monitor omega-3 fatty acid intake (diet, over-the-counter supplements, prescription medication)

Clinical Background

Omega-3 fatty acids, also called n-3 polyunsaturated fatty acids (n-3 PUFAs), are involved in multiple biological pathways, including coagulation, muscle function, cellular transport, and cell division and growth. The 3 major omega-3 fatty acids are eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid. Fish oil and fatty fish such as salmon, mackerel, herring, and tuna are the primary dietary sources of EPA and DHA. Alpha-linolenic acid is found in plant-based foods such as green leafy vegetables, beans, and vegetable oils; it is metabolized to EPA and then, though very inefficiently, to DHA after being ingested.1,2

A diet rich in omega-3 fatty acids is associated with a decreased risk of cardiovascular events, including sudden cardiac death; studies are summarized by De Caterina.3 The American Heart Association4 and the European Society for Cardiology5 recommend dietary intake of omega-3 fatty acids to reduce cardiovascular disease risk. Up to 4 g/d of purified omega-3 fatty acids are considered safe,6 but higher levels have not been thoroughly tested in clinical trials.

Although intake of omega-3 fatty acids is related to cardiovascular risk, EPA and DHA measurements can provide a more accurate prediction of clinical events.7 The sum of EPA and DHA, expressed as a percentage of total phospholipid fatty acids, is called the omega-3 index.8 The index can be used as an indicator of risk for sudden cardiac death and nonfatal cardiovascular events and as a therapeutic target.7 It can also be used to assess adherence to omega-3 therapy and/or success or failure of such therapy.

In contrast to omega-3 fatty acids, omega-6 fatty acids (eg, arachidonic acid [AA]) and their metabolites are more proinflammatory than anti-inflammatory. Two proposed markers of cardiovascular risk incorporate both omega-3 and omega-6 fatty acids: the omega-6/omega-3 ratio and the EPA/AA ratio. The omega-6/omega-3 ratio is still used by some physicians, but the clinical utility of the ratio has been called into question; see Harris for a review.9 One drawback of the ratio is that it does not differentiate fatty acids that have different physiologic properties (eg, effect on platelet function and lowering triglycerides).9 Recent data indicate that the EPA/AA ratio, which includes specific types of omega-3 and omega-6 fatty acids, can be a useful alternative.8,10 Higher EPA/AA ratios are associated with lower cardiac risk.10

This test provides measurements of EPA, DHA, and AA. The report also includes the omega-3 index, the omega-6/omega-3 ratio, and the EPA/AA ratio.

Individuals Suitable for Testing

  • Individuals who are being considered for omega-3 therapy (eg, those with hypercholesterolemia and/or hypertriglyceridemia and those at high risk of cardiovascular disease)

  • Individuals being treated with omega-3 supplementation


  • Liquid chromatography, tandem mass spectrometry (LC/MS/MS) measurement of EPA, DHA, and AA, which are reported as a percentage of total phospholipid fatty acids (PLFAs); total PLFA measurement includes the 21 highest concentration fatty acids (C14 through C24) present in plasma phospholipids

  • Calculations
    –  Omega-3 index = [(EPA + DHA) ÷ total PLFA] x 100
    –  Omega-6/omega-3 = sum of 6 omega-6 fatty acids ÷ sum of 3 omega-3 fatty acids
    –  EPA/AA = % EPA ÷ % AA
  • Analytical sensitivity
    –  EPA:
    –  DHA:
    –  AA:

Reference Range

Omega-3 index: 1.4-4.9%
Omega-6/omega-3 (ratio): 5.7-21.3
EPA/AA (ratio): ≤0.2
EPA: 0.2-1.5%
DHA: 1.2-3.9%
AA: 5.2-12.9%

Reference ranges reflect the middle 95th percentile range derived from normal individuals tested with this assay.

Interpretive Information

The cardiovascular disease risks associated with omega-3 indices are shown in the Table. The risks are based on data, stratified into quartiles, derived from normal individuals tested with this assay. Population-based studies have shown that individuals in the lowest quartile are at high risk, those in the second and third quartiles are at moderate risk, and those in the highest quartile are at lowest (ie, optimal) risk.11,12

Table. Interpretation of Omega-3 Index Scores
Omega-3 Index

Cardiovascular Disease Risk Level







Consumption of foods high in omega-3 fatty acids (EPA and DHA), dietary supplements containing omega-3 fatty acids, and prescription omega-3 fatty acids can increase the omega-3 index. An omega-3 index below the desired target in treated individuals suggests 1) an inadequate increase in dietary omega-3 fatty acids; and/or 2) patient noncompliance or an inadequate dosage of supplements or prescription omega-3.

A higher EPA/AA ratio is associated with lower risk for major coronary events (sudden cardiac death, fatal or nonfatal myocardial infarction, unstable angina pectoris with myocardial ischemia, or the need for revascularization procedures).10


  1. Brenna JT, Salem N Jr, Sinclair AJ, et al. alpha-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fatty Acids. 2009;80:85-91.

  2. Kris-Etherton PM, Taylor DS, Yu-Poth S, et al. Polyunsaturated fatty acids in the food chain in the United States. Am J Clin Nutr. 2000;71:179S-188S.

  3. De Caterina R. n-3 fatty acids in cardiovascular disease. N Engl J Med. 2011;364:2439-2450.

  4. Smith SC Jr, Benjamin EJ, Bonow RO, et al. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011;124:2458-2473.

  5. Perk J, De Backer G, Gohlke H, et al. European guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012;33:1635-1701.

  6. Lovaza [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2014.

  7. von Schacky C. Omega-3 fatty acids vs. cardiac disease—the contribution of the omega-3 index. Cell Mol Biol (Noisy-le-grand). 2010;56:93-101.

  8. Superko HR, Superko SM, Nasir K, et al. Omega-3 fatty acid blood levels: clinical significance and controversy. Circulation. 2013;128:2154-2161.

  9. Harris WS. The omega-6/omega-3 ratio and cardiovascular disease risk: uses and abuses. Curr Atheroscler Rep. 2006;8:453-459.

  10. Itakura H, Yokoyama M, Matsuzaki M, et al. Relationships between plasma fatty acid composition and coronary artery disease. J Atheroscler Thromb. 2011;18:99-107.

  11. Albert CM, Campos H, Stampfer MJ, et al. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med. 2002;346:1113-1118.

  12. Siscovick DS, Raghunathan TE, King I, et al. Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest. JAMA. 1995;274:1363-1367.

Content reviewed 08/2015


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